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Tuesday, 11/15/2016 11:47:19 AM

Tuesday, November 15, 2016 11:47:19 AM

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Importance of Wolchok’s remarks in yesterday’s PR. The key to partnerships comes from Wolchok’s confirmation that Bavi “creates a more immune active environment in which other treatments are able to have greater anti-tumor impact.”

Look how this remark echoes and reinforces comments by Dr. Perlmutter, head of IO research at Merck, in an October ESMO article on Keytruda vs. Opdivo. Dr. Perlmutter explained that higher levels of PD-L1 confer a greater benefit from PD-1 blockers and “It turns out PD-L1 expression is just a marker for the presence of an immune response.” Here is a quote from the article:

So what does PD-L1 expression mean — and why do higher levels confer a greater benefit from PD-1 blockers?

"It turns out PD-L1 expression is just a marker for the presence of an immune response," explained Merck's head of research, Dr. Roger Perlmutter. "Expression of PD-L1 is increased by immune response factors."

In English: PD-L1 is a signal that the immune system has been trying to fight the cancer. Or, as Perlmutter puts it, "Gee, there's already an immune response going on here."


http://www.cnbc.com/2016/10/07/bristol-myers-mercks-lung-cancer-treatments-square-off-this-weekend.html

This is why Wolchok’s comment yesterday is so important when he confirmed that Bavi’s MOA is to “create a more immune active environment”:

Dr.Jedd.Wolchok states, “Based on these study results, we believe that the targeting of PS is having meaningful activity within the tumor microenvironment in the B16 melanoma model. It appears that this activity creates a more immune active environment in which other treatments, including radiation, are able to have a greater anti-tumor impact.



The really important part of the MSK poster, the part that will wake up all the BP decision makers, is not the mice survival data but rather all the detailed work MSK did to confirm that Bavi is indeed triggering an upstream immune response, e.g. increase in CD8 T-cells, shift of macrophage from M2 to M1. MSK summarizes this “creation of a more active immune environment” in the 3rd and 4th bullet points of the Poster Conclusion. This is just what Dr. Perlmutter at Merck said was missing in the 80% of patients that don’t respond to PD-1. To quote Perlmutter, Keytruda and Opdivo work better when the clinician can say "Gee, there's already an immune response going on here."

There is now strong evidence from the MSK poster and Wochok’s summary comments that Bavi triggers an upstream immune response. This will be a huge boost to the ongoing partnership talks.
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